Previous methods employing surgical deafferentation or sensory deprivation have been valuable in establishing present concepts about neuronal interdependence but have not specifically addressed the role which axon transport, as well as function, may play in mediating this important activity. Using the visual pathway of the developing and mature rat as a model, colchicine and xylocaine, agents which interrupt axon transport, will be applied to the cell bodies of the primary afferent pathway by intraocular injection in graded doses. During the first year of the project, the effects of this procedure upon the retina and optic nerve will be examined by quantitative light and electron microscopic techniques. Rates of axon transport in the optic nerve and tract will be measured by injections of 3H amino acids followed by standardized liquid scintillation counting methods and autoradiography. The second year will be occupied by an analysis of several parameters of responses in the lateral geniculate nucleus and the superior colliculus following intraocular injection. Rapid Golgi and Golgi-Cox impregnations should demonstrate alterations in dendrite length, branching, reorientation and changes in distribution and numbers of spinous protrusions. Cell population density and individual ultrastructural patterns will be measured, analyzed and related to induced alterations in retinofugal synaptic arrays. Adaptive plastic responses following this type of pharmacologic manipulation will be searched for and, if present, analyzed. Finally, the third year will be devoted to a light and electron microscopic analysis of the visual cortex with specific emphasis upon alterations in neuronal cell population and synaptic density changes in thickness of individual cortical layers, and a precise quantitative analysis of stellate and pyramidal cells with reference to dendrite reorientation and spine populations.